Levosimendan in paediatric cardiac anaesthesiology: A systematic review and meta-analysis.

This paper is a systematic review to assess the safety and efficacy of levosimendan use in paediatric cardiac surgery. It was done by the anaesthesiology department of Leuven, Belgium.


Levosimendan is a calcium sensitizer which has been around for a number of years and never really found a niche. In my PICU practice it is used predominately in patients with severe heart failure to help get them off inotropic support. It has been studied in adult cardiac surgical patients but was not found to be of clinical benefit and there have been conflicting results in its ability to improve some measured indices of cardiac function.
It is expensive (> $1000 per ampoule).
It is a powerful dilatator and some investigators have postulated that this is its major action in increasing cardiac output. This effect can be detrimental in the postoperative cardiac patient, and when giving it to patients in severe heart failure, it is not uncommon that they require a vasopressor to maintain an acceptable MAP.

What the metanalysis showed

The study included 9 RCTs which had around 50 patients in each (range 20-187), and compared levosimendan with milrinone, 2 compared it with placebo and 1 with dobutamine.
In 4 studies, the primary outcome was the incidence of low cardiac output syndrome (LCOS) and levosimendan did show a significant reduction in LCOS compared with other inotropes.
No study had any clinical outcome as the primary outcome, though most had a number of clinical outcomes as the secondary outcomes.
There was no comparative group difference in mortality, ICU length of stay, hospital length of stay, duration of ventilation, serum lactate, central venous saturation, nor serum creatinine.
Cardiac index was looked at in 4 studies and did show an improvement with levosimendan.
The authors rightly conclude from the metanalysis that levosimendan decreases the incidence of LCOS and increases cardiac index but has no effect on clinical outcome.
The discussion includes reporting of the adult studies which have shown no clinical benefit with many of them not even showing an increase in cardiac index.
There are a number of hypotheses raised as to why the drug showed no clinical benefit – inadequate dosing, heterogenous population, differences in LCOS definitions, inaccuracy in measurement of cardiac output.

Issues with the paper

Without providing evidence, the authors state that there were no major side effects. There is no data on safety even though that was a stated aim of the metanalysis.
The tone of the paper reads as if the authors are pro the drug and are looking for reasons why the metanalysis showed that it doesn’t work.
Inconsistency between studies around definition of LCOS. This is hampered by the fact that LCOS is a common and transient condition that often resolves over 12-24 hours postoperatively.
A statement that inotropes cause excess mortality is very controversial.

Take Home Message

Levosimendan does not improve clinical outcomes in paediatric cardiac surgical patients.
Problems related to levosimendan not mentioned in the paper are:
1. Needs to be given over a number of hours (we give over 24 hours and if using in surgical patients would begin the infusion the night before surgery).
2. Severe vasodilatation is common (this would be a major issue post cardiac surgery)
3. It is expensive.
I would not use it in my practice around the time of operation. I may consider using it in patients stuck on inotropes with very poor cardiac function postoperatively.

Reviewed by Dr David Buckley